27354-77-4Relevant academic research and scientific papers
Synthesis of new thiazole-2, -4, and -5-yl-(amino)methylphosphonates and phosphinates: Unprecedented cleavage of thiazole-2 derivatives under acidic conditions
Olszewski, Tomasz Krzysztof,Boduszek, Bogdan
experimental part, p. 8661 - 8666 (2011/01/04)
An efficient and reliable synthesis of new thiazole-(amino) methylphosphonic, phosphinic acids, and phosphine oxides is reported. The synthetic protocol is based on nucleophilic addition of phosphorous species to thiazole derived imines. Unexpectedly, it was discovered that heating of thiazole-2-yl-(amino)methylphosphonates and phosphinates with aqueous HCl leads to their decomposition resulting in a rupture of the C-P bond, rejecting of the phosphorus containing fragment and formation of the corresponding secondary N-(thiazole-2-yl-methyl)-alkylamines. Two alternative mechanisms for this cleavage are postulated.
Second-generation peptidomimetic inhibitors of protein farnesyltransferase demonstrating improved cellular potency and significant in vivo efficacy
O'Connor, Stephen J.,Barr, Kenneth J.,Wang, Le,Sorensen, Bryan K.,Tasker, Andrew S.,Sham, Hing,Shi-Chung, Ng,Cohen, Jerome,Devine, Edward,Cherian, Sajeev,Saeed, Badr,Zhang, Haichao,Jang Yun, Lee,Warner, Robert,Tahir, Stephen,Kovar, Peter,Ewing, Patricia,Alder, Jeffrey,Mitten, Michael,Leal, Juan,Marsh, Kennan,Bauch, Joy,Hoffman, Daniel J.,Sebti, Said M.,Rosenberg, Saul H.
, p. 3701 - 3710 (2007/10/03)
The synthesis and evaluation of analogues of previously reported farnesyltransferase inhibitors, pyridyl benzyl ether 3 and pyridylbenzylamine 4, are described. Substitution of 3 at the 5-position of the core awl ring resulted in inhibitors of equator less potency against the enzyme and decreased efficacy in a cellular assay against Ras processing by the enzyme. Substitution of 4 at the benzyl nitrogen yielded 26, which showed improved efficacy and potency and yet presented a poor pharmacokinetic profile. Further modification afforded 30, which demonstrated a dramatically improved pharmacokinetic profile. Compounds 26 and 29 demonstrated significant in vivo efficacy in nude mice inoculated with MiaPaCa-2, a human pancreatic tumor- derived cell line.
